ASH 2023 | Patient-reported outcomes in CARTITUDE-4: cilta-cel vs SoC in R/R multiple myeloma

So the Phase III CARTITUDE-4 study is a randomized study exploring cilta-cel and comparing cilta-cel, a BCMA targeting agent, versus standard of care treatment for patients with relapsed/refractory myeloma refractory to lenalidomide after 1 to 3 prior lines of therapy. And the primary results of this study were presented at the last ASCO/EHA meeting and were published in The New England Journal of Medicine, where the progression-free survival, which was the primary endpoint of this study, was met. And at this ASH meeting, we have presented the analysis of patient-reported outcomes of patients that were enrolled in the CARTITUDE-4 study, at a median follow-up of 15.9 months. 

So, investigators administered PROs to patients that were enrolled in the study at different time points, baseline and then throughout the study every three months, and then up to month 24. And the PROs used were the EORTC Quality of Life questionnaire, which is a cancer-specific questionnaire assessing global health status and then symptoms and functioning domains. Then the EuroQol life questionnaire, including a visual analog scale where patients self-rate their health, and then the MySIm-Q questionnaire, which is a myeloma disease-related questionnaire, which was specifically designed in patients with multiple myeloma, assessing several symptoms and items related to multiple myeloma. 

So what we found out was that the patients in the cilta-cel arm reported a greater improvement in their global health status score, defined by the EORTC quality of life questionnaire, meaning that patients in the cilta-cel arm experienced a greater improvement in their general health. Patients also reported a greater improvement as compared to patients treated in the standard of care arm in terms of emotional functioning, but also social role and physical functioning, meaning that patient reported to feel less stressed, less irritable, less depressed during the study, as compared to patients in the standard of care, in which neither of these items actually improved. When patients were asked also to self-rate their health through the visual analog scale, we observed greater scores, a greater improvement, in terms of self-rated health for patients in the cilta-cel arm, when at month 12, the improvement reached a clinically meaningful improvement, as compared to the standard of care arm in which patients did not report an overall improvement, the PRO values remained basically similar to the to the values at baseline. 

And also we investigated pain and fatigue, and there was an improvement in pain for both treatment arms, cilta-cel and the standard of care, but the improvement was greater in terms of pain in the cilta-cel arm. This improvement was very quick to occur at month three already and remained constant throughout the follow-up at month 12. And importantly, there was an improvement also in fatigue for cilta-cel, while we did not observe any significant changes in the fatigue scores for patients in the standard of care arm. And a greater proportion of patients in the cilta-cel arm reported a significant, meaningful improvement from baseline in terms of both pain and fatigue as compared to patients in the standard of care arm. 

[Finally] also in terms of myeloma-related symptoms and impacts. We observed an improvement in the cilta-cel arm in both domains, in symptoms and impacts, while we did not observe a significant improvement for patients in the standard of care arm. And eventually the time to symptom worsening, sustained symptom worsening, was longer in the cilta-cel arm, and this is consistent with the longer progression-free survival reported already in the primary analysis, as compared to the time to symptom worsening in the standard of care arm. 

So altogether, these results in which patient reported a greater global health status improvement, a great improvement in the self-rated through the visual analog scale, a greater improvement in terms of emotional functioning, but also physical, social, and emotional functioning, and improvement also in pain, in fatigue and in symptoms related to multiple myeloma, along with the PFS benefit, the benefit in terms of response rate and MRD-negativity rates already reported in the primary analysis. All together, these results reinforce the potential role for cilta-cel to be a new standard of care in patients with lenalidomide-refractory multiple myeloma after at least one prior line of therapy.